The evolution of strains of cells or organisms resistant to currently effective therapeutic agents is an ongoing medical problem. For example, the development of cancerous cells resistant to certain anti-proliferative agents, for example, chemotherapeutic drugs, has long been recognized as a problem in the oncology field. Once resistant cells develop, the therapeutic regime must be modified to introduce other, effective anti-proliferative agents. Another example of resistance is the development of strains of microbial, fungal, parasitic and viral pathogens resistant to one or more anti-infective agents. This problem of resistance to anti-infective agents is particularly problematic for antibiotic therapy. Over the past several decades, there has been an increase in incidence of bacteria that have developed resistance to one or more antibiotic agents. Because of these resistance problems, there is a need for new anti-proliferative and anti-infective agents that are effective against strains of cells or organisms that have developed resistance to currently available agents.
In the field of anti-infective agents, a variety of different agents having antibiotic and other properties have been developed over the years and approved for use in mammals and other animals. For example, one such substance is cycloheximide, which is an antibiotic produced by the streptomycin-producing strains of Streptomyces griseus. Cycloheximide corresponds to the chemical formula C15H23NO4 and is also known as [1S-[1α(S*),3α,5β]]-4-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]-2,6-piperidinedione, naramycin A, and Actidione (See, The Merck Index, 13 Edition, entry 2757, 2001). A chemical representation for cycloheximide is as shown below.

Cycloheximide has long been available for use as an anti-infective agent active against eukaryotic pathogens, including fungi. However, cycloheximide is toxic to mammals, and it does not inhibit bacterial growth. Accordingly, cycloheximide has not been used to treat bacterial infections, and has only been used to treat fungal infections on a limited basis. Nevertheless, the structure of cycloheximide bound to a large ribosomal subunit is useful in the discovery of new anti-fungal and anti-bacterial agents. For example, the differences between bacterial, fungal, and human ribosomes that bind cycloheximide, together with the structure of cycloheximide bound to a large ribosomal subunit, can guide the discovery of novel chemical entities useful in treating fungal and bacterial infections in humans.
Accordingly, there is still an ongoing need for new analogs and derivatives of cycloheximide that are effective as anti-infective, anti-proliferative, or anti-inflammatory agents.